We are studying the genetic basis of a variety of skin disorders, including epidermolytic hyperkeratosis, lamellar ichthyosis and congenital ichthyosiform erythroderma, Darier's disease, Hailey-Hailey disease, erythrokeratodermia variabilis, white sponge nevus, Sjogren-Larsson syndrome and Gorlin syndrome. Patients and their families are recruited for study. They travel to the NIH clinics (or rarely we travel to them) to enable our research group to perform detailed family and medical histories, skin examinations, skin biopsies, phlebotomy, and clinical photography. DNA is extracted from patient's and family member's buccal cells. Skin samples are used to confirm diagnoses and to investigate ultrastructural abnormalities specific to each disease. Clinical heterogeneity (different clinical appearances of the "same" disease) is investigated using the information collected. DNA-based polymorphisms are used for linkage studies to determine the chromosomal location of the skin disease locus. Identification of the disease-causing gene is made by searching for mutations in candidate genes in the mapped regions. Genotype-phenotype correlations are drawn based on the clinical presentation and the specific gene mutation.